Methods for treating pervasive development disorders

ABSTRACT

A method of utilizing the chymotrypsin level of an individual as a measure of the success of secretin, other neuropeptides, and peptides or digestive enzyme administration to such individuals, and in particular, as a prognosticative of potential secretin, other neuropeptides, peptides, and digestive enzyme administration for persons having ADD, ADHD, Autism and other PDD related disorders. In one aspect, a method for determining the efficacy of secretin, other neuropeptides, peptides, or digestive enzymes for the treatment of an individual diagnosed with a pervasive developmental disorder (PDD) comprises obtaining a sample of feces from an individual, determining a quantitative level of chymotrypsin present in the sample, and correlating the quantitative level of chymotrypsin determined to be present in the sample with the PDD to determine the efficacy of treating the individual with secretin, other neuropeptides, peptides, or digestive enzyme administration. In another aspect, a therapeutic method for treating an individual diagnosed with a PDD pervasive developmental disorder comprises determining the efficacy of secretin, other neuropeptides, peptides, and digestive enzyme administration for the treatment of the individual based on a measure of the individual&#39;s chymotrypsin level, and administering secretin, other neuropeptides, peptides, or digestive enzymes to the individual based on the determination of the measure of the individual&#39;s chymotrypsin level.

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application is a Continuation-in-Part of U.S. patentapplication Ser. No. 09/466,559, filed on Dec. 17, 1999.

BACKGROUND

[0002] 1. Technical Field

[0003] The present invention relates generally to a method for treatingindividuals diagnosed with a form of PDD (pervasive developmentdisorder) and other disorders such as ADD (attention deficit disorder)and ADHD (attention deficit hyperactivity disorder). More specifically,the present invention is directed to therapeutic method for treatingindividuals with such disorders by administering secretin, otherneuropeptides, peptides, and/or digestive enzymes, as well as aprognosticative method for determining the potential effectiveness ofthe administration of secretin, other neuropeptides, peptides, and/ordigestive enzymes for the treatment of such disorders.

[0004] 2. Description of Related Art

[0005] PDDs are a class of disorders defined by both American andInternational diagnostic systems (i.e., the Diagnostic and StatisticalManual of Mental Disorders, 4th edition (DSM-IV) and World HealthOrganization: International Classification of Diseases, Tenth revision(ICD-10)). The spectrum of PDDs include disorders such as Autism,Aspergers, ADD, and ADHD. PDDs are typically characterized by multipledistortions in the development of basic psychological functions that areinvolved in the development of social skills and language, such asattention, perception reality testing and motor movement. In addition,many children diagnosed with Autism, for example, suffer from primarydiffuse gastrointestinal problems such as protracted diarrhea andconstipation. Although PDDs are currently of unknown etiology, manyconventional methods, such as dietary alteration, behavioralmodification, and medication, have been utilized for treatingindividuals suffering from PDD related disorders. Unfortunately, PDDrelated disorders have no known treatment beyond that which issymptomatic, and these conventional methods have proven unsuccessful inallowing such children and adults to become symptom, or disorder free.

[0006] A child which displays signs of developmentally inappropriateinattention, impulsivity and hyperactivity is typically diagnosed ashaving ADD and/or ADHD. With these disorders, there can be markeddisturbances of organization, distractibility, impulsivity,restlessness, and other disturbances of language and/or social behavior.A combination of psychiatric care and medicine is typically used fortreating children with ADD and ADHD.

[0007] It was recently discovered that the administration of secretin, agastrointestinal peptide hormone, to children diagnosed with Autismresulted in ameliorating the symptoms associated with Autism. Thisfinding was published in the article by Horvath et al., entitledImproved Social and Language Skills After Secretin Administration InPatients with Autistic Spectrum Disorders, Journal of the Associationfor Academic Minority Physician Vol.9 No.1, pp. 9-15, January, 1998. Thesecretin administration, as described in Horvath, was performed as adiagnostic procedure, i.e., to stimulate pancreaticaobiliary secretionduring an upper gastrointestinal endoscopy, rather than as a therapeuticprocedure. Although the specific mechanism by which the secretinimproved the autistic-related symptoms was not specifically identified,Horvath postulated that secretin may have had a direct or indirecteffect on the central nervous system. What is important, however, isthat this was the first time that gastrointestinal problems of autisticchildren were linked to a possible etiology in Autism.

[0008] Accordingly, in view of such findings, a method for determiningwhether an individual suffering from a disorder in the PDD spectrum willbenefit from the administration of secretin, other neuropeptides,peptides and/or digestive enzymes, as well as a therapeutic method fortreating such individuals with the administration of secretin, otherneuropeptides, peptides and/or digestive enzymes, are highly desired.

SUMMARY OF THE INVENTION

[0009] The present invention is directed to a method of analyzing thechymotrypsin level of an individual to determine the potential benefitof the administration of secretin, other neuropeptides, peptides and/ordigestive enzyme administration to such individual, and in particular,as a prognosticative of potential secretin, other neuropeptides,peptides, and/or digestive enzyme administration for individualsdiagnosed as having ADD, ADHD, Autism and other PDD related disorders.

[0010] In one aspect, a method for determining the efficacy of secretin,other neuropeptides, peptides, or digestive enzymes for the treatment ofan individual diagnosed with a pervasive developmental disorder (PDD)comprises obtaining a sample of feces from an individual, determining aquantitative level of chymotrypsin present in the sample, andcorrelating the quantitative level of chymotrypsin determined to bepresent in the sample with the PDD to determine the efficacy of treatingthe individual with secretin, other neuropeptides, peptides, ordigestive enzyme administration.

[0011] In another aspect, a therapeutic method for treating anindividual diagnosed with a PDD pervasive developmental disordercomprises determining the efficacy of the administration of secretin,other neuropeptides, peptides, and digestive enzyme for the treatment ofthe individual based on a measure of the individual's chymotrypsinlevel, and administering secretin, other neuropeptides, peptides, ordigestive enzymes to the individual based on the determination of themeasure of the individual's chymotrypsin level.

[0012] The present invention involves determining the presence ofabnormal protein digestion of individuals, especially children, bymeasuring the chymotrypsin levels so as to determine if the individualis likely to benefit from the administration of secretin, digestiveenzymes, peptides and/or neuropeptides. Although there have been methodsto test fecal samples for indications of cystic fibrosis and pancreaticdiseases in infants, none of the known methods have tested fecal samplesin determining the benefits of administering secretin, otherneuropeptides, peptides and/or digestive enzymes to individualssuffering from a PDD. Indeed, in so far as an individual's fecalchymotrypsin level is a broad measure of protein and fat digestion, suchlevels can be applied to all those who may benefit from improvements inthis mode of digestion. Furthermore, as low measures of fecalchymotrypsin expresses an abnormality of protein digestion, it ispostulated that an improvement of protein digestion to promote normalgrowth and development of an individual suffering from a PDD by theadministration of secretin, other neuropeptides, peptides and/ordigestive enzymes, can ameliorate the symptomatologies of PDDs.

[0013] Accordingly, in another aspect of the present invention, atherapeutic method is provided for treating an individual diagnosed witha PDD including but not limited to Autism, Aspergers, ADD and ADHD,comprising the steps of:

[0014] determining the effectiveness of secretin administration for thetreatment of the individual based on a measure of the individual'schymotrypsin level; and

[0015] administering secretin therapy to the individual based on thedetermination of the measure of the individuals chymotrypsin level.

[0016] In yet another aspect, the therapeutic method involvesadministering a fecal chymotrypsin test to measure an individual's fecalchymotrypsin level. Preferably, an enzymatic spectrophotometry method isused for measuring the fecal chymotrypsin level of the individual. Upondeterminating that an individual has an abnormal level of chymotrypsin,the individual is preferably administered 1 U/kg of body weight ofporcine or human secretin by means of an intravenous push method. Thismethod can be described as the administration of an IV push of salinesolution and secretin to equal 1 U/kg of body weight. The individualthen receives 1 unit test dose (absolute). A period of one minute isallowed to pass to determine if the individual has any allergicreactions to the secretin. After one minute has elapsed, if nourticarial reaction or any other allergic reaction has occurred, theremainder of the dose is administered. Subsequent fecal chymotrypsinsamples are then gathered at one week intervals post administration todetermine any changes in the chymotrypsin levels.

[0017] These and other aspects, features and advantages of the presentinvention will be described and become apparent from the followingdetailed description of preferred embodiments, which is to be read inconnection with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1 illustrates the overall net change in results of a CARStest (Childhood Autism Rating Scale) depicting behavior of 16 autisticchildren pre-secretin and post-secretin administration, where the solidlines indicate pre-secretin scores and the dotted lines indicatepost-secretin scores;

[0019]FIG. 2 illustrates percentage change from pre-secretin topost-secretin administration in the average scores of the respectivecomponents of the CARS test of FIG. 1;

[0020]FIG. 3 illustrates the change in CARS scores for the sub-classVisual response from pre-secretin administration to three weekspost-secretin administration, where the solid lines indicatepre-secretin scores and the dotted lines indicate post-secretin scores;

[0021]FIG. 4 illustrates the change in CARS scores for the sub-classVerbal Skills from pre-secretin administration to three weekspost-secretin administration, where the solid lines indicatepre-secretin scores and the dotted lines indicate post-secretin scores;

[0022]FIG. 5 illustrates the change in CARS scores for the sub-classTouch/Taste/Smell from pre-secretin administration to three weekspost-secretin administration, where the solid lines indicatepre-secretin scores and the dotted lines indicate post-secretin scores;

[0023]FIG. 6 illustrates the change in CARS scores for the sub-classObject Use from pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

[0024]FIG. 7 illustrates the change in CARS scores for the sub-classListening from pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

[0025]FIG. 8 illustrates the change in CARS scores for the sub-classImitation from pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

[0026]FIG. 9 illustrates the change in CARS scores for the sub-classBody Use from pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

[0027]FIG. 10 illustrates the change in CARS scores for the sub-classAdaptation to Change from pre-secretin administration to three weekspost-secretin administration, where the solid lines indicatepre-secretin scores and the dotted lines indicate post-secretin scores;

[0028]FIG. 11 illustrates the change in CARS scores for the sub-classActivity Level from pre-secretin administration to three weekspost-secretin administration, where the solid lines indicatepre-secretin scores and the dotted lines indicate post-secretin scores;

[0029]FIG. 12 illustrates the change in CARS scores for the sub-classGeneral Impression from pre-secretin administration to three weekspost-secretin administration, where the solid lines indicatepre-secretin scores and the dotted lines indicate post-secretin scores;

[0030]FIG. 13 illustrates the measured fecal chymotrypsin levels of 16autistic children pre-secretin administration;

[0031]FIG. 14 illustrates the measured fecal chymotrypsin levels of the16 autistic children approximately one week post-secretinadministration;

[0032]FIG. 15 illustrates the measured fecal chymotrypsin levels of 28ADD children;

[0033]FIG. 16 illustrates the measured fecal chymotrypsin levels of 34ADHD children; and

[0034]FIG. 17 illustrates Ritalin levels administered before and aftersecretin administration in five of the ADHD children in FIG. 16, wherethe shaded bars indication pre-secretin Ritalin levels and thenon-shaded bars indicate post-secretin Ritalin levels.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0035] The present invention is directed to a method of analyzingchymotrypsin levels in persons, especially children, as a measure of thesuccess of administering secretin, other neuropeptides, peptides and/ordigestive enzymes for the therapeutic treatment of ADD, ADHD, Autism,Aspergers and other PDD related disorders. The use of secretin for thetreatment of Autism is presently in the investigational stages. When thepositive affects of the neuropeptide secretin on childhood autism werefirst discovered and published, research was conducted by the presentinventor to formulate a process that would enable one to definitivelydetermine if individuals, especially children, having a PDD could betested prior to the administration of secretin for its possible efficacyfor treating PDD. Tests were performed to measure the fecal chymotrypsinlevels (referred to herein as Fecal Chymotrypsin Test) in children whospan the entire PDD spectrum and whose symptomotology place them in thisDSM IV category. As demonstrated below, such tests revealed that amajority of the children diagnosed with autism, ADD and ADHD, forexample, had abnormal chymotrypsin levels. It is believed that suchabnormal levels of chymotrypsin have not heretofore been identified inthe PDD population of children and adults.

[0036] It is postulated that the abnormal levels of chymotrypsin are dueto the inability of the pancreas to release bicarbonate ions, due to thelack of secretin mechanization in the small intestines. The smallintestine has a pH in the range of 1.0-1.5 when the bolus of food entersthe small intestines. Normally, plasma concentrations of secretinincrease when the duodenal pH is below 4.5, and typically doubles duringthe postprandial period. The s cells in the proximal portion of thesmall intestines release secretin in response to this low pH. Thesecretin is then released into the bloodstream and ultimately reachesthe pancreas. In response, the pancreas releases bicarbonate ions, waterand electrolytes into the small intestines thus neutralizing the pH bybringing it from a 1.0-1.5 to approximately 6.5.

[0037] Following this, the pancreas secretes the enzyme trypsin in aninactive form trypsinogen. The trypsinogen is converted to trypsin inthe small intestines. In an environment where the pH is 6.5 or greater,the trypsin catalyzes the formation of chymotrypsinogen to chymotrypsin.These enzymes are essential for the digestion of protein. In the absenceof protein digestion, the amino acids necessary for the growth anddevelopment of individuals are absent. Therefore, based on testsperformed by the present inventor, it is postulated that the increase ofprotein digestion of an individual suffering from PDD can lead to theimprovement of such disorders. Accordingly, since secretin isresponsible for aiding in the protein digestion process, it has beendetermined that the presence of abnormal protein digestion inindividuals, especially children, is indicative of which individuals arelikely to benefit from the administration of secretin.

[0038] Indeed, in accordance with the present invention, experimentalresults have shown that the potential benefit of administering secretin,other neuropeptides, peptides and/or digestive enzymes to individualsdiagnosed with developmental disorders falling within the entirespectrum of PDD may be predetermined by analyzing the measured fecalchymotrypsin levels of such individuals. More specifically, asillustrated below, it has been determined that sub-normal to abnormallevels of fecal chymotrypsin in children/adults with PDD symptoms willbenefit from the administration of secretin, other neuropeptides,peptides and/or digestive enzymes. In addition, experimental tests bythe present inventor have revealed that the administration of secretin,other neuropeptides, peptides and/or digestive enzymes to others beyondthose of who are autistic, especially those diagnosed with ADD and ADHDwill benefit from the administration of secretin, other neuropeptides,peptides and/or digestive enzymes.

[0039] The following experiments describe exemplary diagnosis andtreatment procedures in accordance with the invention. It is to beunderstood that these experiments and corresponding results are setforth by way of illustration only, and nothing therein shall beconstrued as a limitation on the overall scope of the invention.

I. Experiment 1

[0040] In this experiment, 16 children diagnosed as having autism wereadministered the following Fecal Chymotrypsin Test in accordance with anembodiment of the invention. First, approximately 2 grams of stool werecollected from each child and placed in a sterile container (although itis to be understood that any quantity of stool may be collected, as 2grams of stool is not a required amount). Each stool sample was thenanalyzed using, e.g., an enzymatic photospectrometry analysis as isknown by those skilled in the art, to determine the level of fecalchymotrypsin in the stool. Although the enzymatic photospectrophotometryprocess is preferred, any suitable conventional method may be used formeasuring the fecal chymotrypsin levels. The measured chymotrypsinlevels of the 16 autistic children are illustrated in FIG. 13.

[0041] After determining the chymotrypsin levels of the stools, each ofthese levels were compared with threshold chymotrypsin levels todetermine if the child was likely to benefit from secretinadministration. By way of example, with the fecal chymotrypsin tests ofthe stool samples being performed at 30° C., normal levels ofchymotrypsin are deemed to lie above 8.4 U/gram, whereas pathologicallyabnormal levels are deemed to lie below 4.2 U/gram. In addition,chymotrypsin levels between 8.4 U/gram and 4.2 U/gram are consideredequivocal, and further testing of the individual's fecal chymotrypsinlevels over a period of time should be performed. It is to be noted thatas shown in FIG. 13, all of the 16 autistic children that were testedhad abnormal levels of fecal chymotrypsin pre-secretin administration.

[0042] Another stool sample was then collected from each child two daysafter the first test and analyzed to determine the chymotrypsin levels.This second test is preferably performed to obtain additionalchymotrypsin measurements to make a more accurate determination. Thosechildren having abnormal levels of chymotrypsin in their stools areconsidered candidates for secretin administration. Other factors thatmay be considered in determining which children are potential candidatesfor secretin administration aside from the fecal chymotrypsin levelsinclude a previously diagnosed history of autism, a history ofgastrointestinal (GI) dysfunction, including any history of protracteddiarrhea or constipation lasting for a weeks or months, as well as aself-limiting diet consisting primarily of carbohydrates.

[0043] Upon determining that a given child was likely to benefit fromsecretin administration based on the results of the fecal chymotrypsintest, the child was administered a CARS (Childhood Autism Rating Scale)test prior to being scheduled for secretin infusion.

[0044] For each of the 16 autistic children tested, a preferred secretininfusion process according to the present invention was performedinvolving the administering of 1 U/kg of body weight of Secretin-Ferringfor a period of nine months at intervals of approximately 6 weeks. Inaddition, another CARS test was administered to each of the 16 autisticchildren 3 weeks post secretin administration to determine if theirautism had changed post infusion.

[0045] A preferred secretin infusion process includes the initial stepof prepping an arm of the candidate child with an IV injection ofsaline. A test dose of 1U of Secretin-Ferring is then administered tothe child. Approximately one minute after infusion, the child isexamined for signs of allergic reaction including rash, increased heartrate, and increase of blood pressure. If the child does not display anysigns of allergic reaction, the remaining units of Secretin-Ferring isadministered to the child in the manner of an IV push, which is thenfollowed by a saline flush. Subsequently, each child receives a 1 U/kgof body weight infusion of Secretin-Ferring approximately every 6 weeksfor 9 months. It is to be understood that any commercially availableform of secretin may be used.

[0046] Results of Experiment 1

[0047] The results of Experiment 1 are illustrated in FIGS. 1-14. Forinstance, approximately one week after the first secretin infusion, thefecal chymotrypsin level of each of the 16 autistic children wasmeasured again. The results of this test are illustrated in FIG. 14. Asshown, the chymotrypsin level of each of the 16 autistic children testincreased post-secretin administration (as compared with the levelsshown in FIG. 13).

[0048] In addition, FIG. 1 illustrates the pre-secretin CARS testresults (solid line) and the post-secretin CARS test results (dottedline) for each of the 16 autistic children tested approximately 3 weeksafter the first secretin administration. Most notably, FIG. 1illustrates an overall decrease in the CARS scores indicatingimprovements in the PDD/autistic symptoms of the children. Inparticular, FIG. 2 illustrates respective percentage decreases incomponents of CARS scores, wherein the numbers represent percentagechange in the average of the scores in each component of the CARS testpost-secretin administration. In particular, FIGS. 3-12 illustrate theimproved scores of each of the 16 autistic children for the individualcomponents of the CARS scores. As shown, the component scoresdemonstrated improvement except for the fear component which increased 3weeks post infusion.

II. Experiment 2

[0049] In this experiment, 37 autistic children with abnormal fecalchymotrypsin levels were administered secretin over the course of 6months using the secretin infusion process described above. Their fecalchymotrypsin (FC) levels were measured weekly using the fecalchymotrypsin test described above.

[0050] Results of Experiment 2

[0051] Out of the 37 autistic children tested, the fecal chymotrypsinlevels of 34 children had returned to normal after 6 months, the fecalchymotrypsin levels of 2 children moved to equivocal, and the fecalchymotrypsin level of 1 child remained abnormal. These results of thisexperiment are listed in the following Table 1. TABLE 1 6 Months Post-Pre-Secretin Secretin Autistic Children Tested AdministrationAdministration # Autistic Children w/ Abnormal FC 37  1 levels #Autistic Children w/ Equivocal FC 0 2 levels # Autistic Children w/normal FC levels 0 34 

III. Experiment 3

[0052] In this experiment, the fecal chymotrypsin levels of 28 childrendiagnosed with ADD were obtained using the fecal chymotrypsin testdescribed above in Experiment 1. FIG. 15 illustrates the measured fecalchymotrypsin levels of these 28 children. It is to be noted that, asshown in FIG. 15, all of the 28 ADD children were found to havesub-normal fecal chymotrypsin levels since all of the values fell below8.4 U/g. More specifically, 8 out of 28 children were determined to havean equivocal fecal chymotrypsin level and 20 out of the 28 children weredetermined to have a pathologic level of fecal chymotrypsin. As notedabove, a chymotrypsin level of 8.4 U/g is considered a reference valuefor normal levels of chymotrypsin.

[0053] Of these 28 children who were diagnosed with ADD and abnormalfecal chymotrypsin levels, 10 were administered digestive enzymescomprising amylase, proteases, lipases, sucrase, maltase, and otherdigestive enzymes. These digestive enzymes were administered one tabletat each mealtime (i.e., three times a day), adjusted for the age andweight of the child. More specifically, for the ADD children ages 1-6, aquantity of digestive enzymes of approximately 4,000-8,000 U.S.P.Units/tablet comprising lipase, amylase and protease were administered.For the ADD children of ages 7-12, a quantity of digestive enzymes ofapproximately 8,000-12,000 U.S.P. Units/tablet comprising lipase,amylase and protease were administered. Other digestive enzymes thatwere administered in smaller quantities included cellulase, sucrase andmaltase. These digestive enzymes were administered over a period of 6months.

[0054] Results of Experiment 3

[0055] At the time of this experiment, 4 out of the 10 children who wereadministered the digestive enzymes were taking Ritalin. As is known inthe art, Ritalin is a stimulant medication used to treat children andadults with ADD and ADHD. More specifically, it is used to treathyperactivity and attention problems. As a result of the administrationof the digestive enzymes, all of the 4 children who had been takingRitalin were able to completely stop taking the Ritalin. In addition,significant improvements in the behavior of the other 6 children werenoted. These results are shown in the following Table 2: TABLE 2 # ADDChildren w/ Sub-normal FC levels 28 # of the 28 ADD Children WithAbnormal FC levels That 10 Were Administered Digestive Enzymes # of the10 ADD Children That Were Administered Digestive  4 Enzymes Who WereTaking Ritalin # ADD Children Requiring Ritalin Administration 6 months 0 Post Administration of Digestive Enzymes

IV. Experiment 4

[0056] In this experiment, the fecal chymotrypsin levels of 34 childrendiagnosed with ADHD were obtained using the fecal chymotrypsin testdescribed above in Experiment 1, the levels of which are illustrated inFIG. 16. As shown, 32 children out of 34 children tested were determinedto have sub-normal fecal chymotrypsin levels. It is to be further notedthat 24 of the 34 children were found to have pathologic levels of fecalchymotrypsin.

[0057] To determine the effect of secretin administration on ADHDchildren, 5 of the 24 children having a pathologic fecal chymotrypsinlevel were administered secretin using the secretin infusion processdescribed above.

[0058] Results of Experiment 4

[0059] The results of this experiment are set forth in FIG. 17, whichillustrates the required levels of Ritalin (in mg) of the 5 childrentested both pre-secretin administration (as indicated by the shadedbars) and 6 months post-secretin administration (as indicated by thenon-shaded bars). It is to be appreciated that as shown in FIG. 17, eachof the 5 children who were administered secretin demonstratedsignificant changes post-secretin administration with respect to thelevel of Ritalin (mg) that each child needed to remain at the samefunctional level as their functional level prior to secretinadministration.

V. Experiment 5

[0060] In this experiment, to determine the effect of the administrationof digestive enzymes to ADHD children, 9 children of the 34 childrendiagnosed with ADHD (in experiment 4 described above) whose fecalchymotrypsin levels were determined to be pathologic were administereddigestive enzymes. Such digestive enzymes included amylase, lipase,proteases, sucrases, maltase, and other digestive enzymes. Each childwas administered 1 tablet of digestive enzymes at each mealtime (i.e.,three times a day), adjusted for age and weight of the child. Morespecifically, for the ADHD children ages 1-6, a quantity of digestiveenzymes of approximately 4,000-8,000 U.S.P. Units/tablet comprisinglipase, amylase and protease were administered. For the ADHD children ofages 7-12, a quantity of digestive enzymes of approximately 8,000-12,000U.S.P. Units/tablet comprising lipase, amylase and protease wereadministered. Other digestive enzymes that were administered in smallerquantities included cellulase, sucrase and maltase. The digestiveenzymes were administered over a 6 month period.

Results of Experiment 5

[0061] It is to be appreciated that as a result of the administration ofdigestive enzymes over the 6 month period, all 9 children were able toreduce their required Ritalin levels. Most notably, 2 of the 9 childrenwere able to stop taking Ritalin after 6 months of digestive enzymeadministration. The results of experiment 5 are illustrated in thefollowing Table 3: TABLE 3 # ADHD Children w/ Abnormal FC levels WhoWere 9 Administered Digestive Enzymes # Of The 9 ADHD Children WhoseRitalin Levels Were 9 Reduced 6 months Post-Digestive EnzymeAdministration # Of The 9 ADHD Children Who Stopped Taking Ritalin 6 2Months Post-Digestive Enzyme Administration

VI. Experiment 6

[0062] The following experiment was performed to determine the effect ofthe administration of digestive enzymes to Autistic children. In thisexperiment, the fecal chymotrypsin levels of 17 autistic children ofvarying ages were measured (pre-digestive enzyme administration) usingthe method described above in Experiment 1. In addition, the fecalchymotrypsin levels of these 17 children were measured 6 months postdigestive enzyme administration after receiving digestive enzyme therapyas described below. The following table demonstrates the measured fecalchymotrypsin levels of these 17 children: TABLE 4 Pre-DE 6-MonthsAdministration Fecal Post-DE Administration Patient Age ChymotrypsinLevels Fecal Chymotrypsin Levels 1 2.5 3.3 7.1 2 7 1.5 3.8 3 9 4.0 7.8 43.5 2.0 10.2 5 5 3.3 8.0 6 4 1.0 6.8 7 8 1.6 10.2 8 6 4.0 12.2 9 7 6.814.9 10  3 2.8 6.2 11  5 3.4 not available 12  3 2.0 4.0 13  2 4.0 4.614  11 3.3 5.0 15  9 2.2 9.2 16  8 1.4 12.0 17  7 3.8 6.0

[0063] As illustrated, each of the 17 autistic children were found tohave either su-normal or pathologic fecal chymotrypsin levels. Inparticular, the fecal chymotrypsin level of patient #9 was found to besub-normal as it fell below 8.4 U/g and the fecal chymotrypsin levels ofthe remaining 16 children were found to be pathologic since the levelsfell below 4.2 U/g.

[0064] Each of the 17 autistic children were administereddigestive/pancreatic enzymes comprising amylases, proteases, lipases,sucrases, maltases, and other digestive/pancreatic enzymes includingtrypsin and chymotrypsin. The digestive enzymes were administered on adaily basis at each mealtime, preferably 3-6 times per day. The quantityof digestive enzymes were adjusted for the weight and ages of the child.For instance, depending on the weight and age of the child, a preferredquantity of lipases ranges from 4,000 - 20,000 U.S.P., a preferredquantity of proteases ranges from 10,000 - 50,000 U.S.P., a preferredquantity of amylases ranges from 10,000 - 60,000 U.S.P., a preferredquantity of pancreatin (pancreatic extract) ranges from 2,000 - 6,000U.S.P., a preferred quantity of chymotrypsin ranges from 2-5 mg and apreferred quantity of trypsin ranges from 60 - 100 mg. In addition, anycombination of two or more types of any of the above digestive enzymesmay be administered.

Results of Experiment 6

[0065] As illustrated in Table 4, the measured fecal chymotrypsin levelsof at least 16 of the 17 autistic children were found to increase 6months post-digestive enzyme administration. Most notably, the fecalchymotrypsin levels of 5 children (patients #4, 7, 8, 15, and 16) thatwere initially found to be pathologic had increased to the normal range6 months post-digestive enzyme administration.

[0066] Furthermnore, a notable decrease in autistic symptomotology ofeach of the 17 autistic children was observed as a result ofdigestive/pancreatic enzyme administration. These observations areoutlined in the following tables. Table 5 outlines the responses thatwere reported after administration of digestive enzymes to the autisticchildren in the range of ages 2-4 (i.e., 6 of the 17 children listed inTable 4). Each numeric entry in Table 5 indicates the number of children(of the 6 children ages 2-4) exhibiting the corresponding behavior.TABLE 5 3 6 Behavior Pre-DE Months Post-DE Months Post-DE some eyecontact 0 2 5 toilet trained 1 2 3 some toilet training 2 3 notavailable (not included above) some speech 2 3 6 formed bowel movement 12 6 hyperactive 5 3 1 plays with others 0 2 4 hand flapping 4 2 1

[0067] Furthermore, Table 6 outlines the responses that were reportedafter administration of digestive enzymes the autistic children of ages5-12 (i.e., 11 of the 17 children listed in Table 4). Again, eachnumeric entry in Table 6 indicates the number of children (of the 11children ages 5-12) exhibiting the corresponding behavior. TABLE 6 3 6Behavior Pre-DE Months Post-DE Months Post-DE some eye contact 8 6 8toilet trained 3 6 6 some toilet training 2 not available 4 (notincluded above) some speech 6 8 10  formed bowel movement 2 7 10 hyperactive 9 5 3 plays with others 3 5 8 hand flapping 6 5 1

[0068] In summary, the results of the experiments described hereindemonstrate that the fecal chymotrypsin level of an individual havingone or more developmental disorders falling within the spectrum of PDDcan be used as a marker to determine the benefit of administeringsecretin, other neuropeptides, peptides and/or digestive enzymes to theindividual. Indeed, the above experiments indicate that theadministration of secretin, other neuropeptides, peptides and/ordigestive enzymes to children suffering from a disorder such as autism,ADD and ADHD, for example, and having sub-normal to pathologic levels offecal chymotrypsin, will result in the amelioration of symptomatologiesof such disorders.

[0069] Although illustrative embodiments have been described herein withreference to the accompanying drawings, it is to be understood that thepresent invention is not limited to those precise embodiments, and thatvarious other changes and modifications may be affected therein by oneskilled in the art without departing from the scope or spirit of theinvention. All such changes and modifications are intended to beincluded within the scope of the invention as defined by the appendedclaims.

What is claimed is:
 1. A method for treating a disorder with secretin,the method comprising the step of administering to an individual havingthe disorder an effective amount of secretin based on the individual'schymotrypsin level to improve a symptom of the disorder.
 2. The methodof claim 1, comprising the steps of: obtaining a sample of feces fromthe individual; measuring a quantitative level of chymotrypsin presentin the sample; and comparing the measured quantitative level with atleast one threshold chymotrypsin level to determine the efficacy ofsecretin administration to the individual.
 3. The method of claim 2,wherein the at least one threshold chymotrypsin level is based on alevel of chymotrypsin associated with at least one other individual ofthe same approximate age that does not have the disorder.
 4. The methodof claim 2, wherein the at least one threshold chymotrypsin level isapproximately 8.4 U/gm.
 5. The method of claim 2, wherein the at leastone threshold chymotrypsin level is approximately 4.2 U/gm.
 6. Themethod of claim 1, wherein the disorder comprises a disorder within aPDD (pervasive developmental disorder) spectrum.
 7. The method of claim1, wherein the disorder comprises autism.
 8. A method for treating adisorder with digestive enzymes, the method comprising the step ofadministering to an individual having the disorder an effective amountof digestive enzymes based on the individual's chymotrypsin level toimprove a symptom of the disorder.
 9. The method of claim 8, comprisingthe steps of: obtaining a sample of feces from the individual; measuringa quantitative level of chymotrypsin present in the sample; andcomparing the measured quantitative level with at least one thresholdchymotrypsin level to determine the efficacy of secretin administrationto the individual.
 10. The method of claim 9, wherein the at least onethreshold chymotrypsin level is based on a level of chymotrypsinassociated with at least one other individual of the same approximateage that does not have the disorder.
 11. The method of claim 9, whereinthe at least one threshold chymotrypsin level is approximately 8.4 U/gm.12. The method of claim 9, wherein the at least one thresholdchymotrypsin level is approximately 4.2 U/gm.
 13. The method of claim 8,wherein the disorder comprises a disorder within a PDD (pervasivedevelopmental disorder) spectrum.
 14. The method of claim 8, wherein thedisorder comprises autism.
 15. The method of claim 8, wherein thedisorder comprises one of ADD (Attention Deficit Disorder) and ADHD(Attention Deficit Hyperactivity Disorder) and both.
 16. The method ofclaim 8, wherein the digestive enzymes comprise a pancreatic enzyme. 17.A method for treating an individual exhibiting a symptom of a PDD(pervasive developmental disorder), the method comprising administeringto the individual an effective amount of digestive enzymes to improveone or more symptoms of the disorder.
 18. The method of claim 17,wherein the disorder comprises autism.
 19. The method of claim 17,wherein the disorder comprises ADD (Attention Deficit Disorder), ADHD(Attention Deficit Hyperactivity Disorder) and both.
 20. The method ofclaim 17, wherein the digestive enzymes comprise a pancreatic enzyme.21. The method of claim 17, wherein the step of administering digestiveenzymes comprises administering a quantitative level of digestiveenzymes on a daily basis based at least on the age of the individual.22. The method of claim 21, wherein the digestive enzymes areadministered three times per day.